RT Journal Article
SR Electronic
T1 A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 217
OP 223
DO 10.21873/cgp.20182
VO 17
IS 3
A1 KENTARO IGARASHI
A1 KEI KAWAGUCHI
A1 NORIO YAMAMOTO
A1 KATSUHIRO HAYASHI
A1 HIROAKI KIMURA
A1 SHINJI MIWA
A1 TAKASHI HIGUCHI
A1 YUTA TANIGUCHI
A1 HIROTAKA YONEZAWA
A1 YOSHIHIRO ARAKI
A1 SEI MORINAGA
A1 SWETA MISRA
A1 SCOTT D. NELSON
A1 SARAH M. DRY
A1 YUNFENG LI
A1 AKIRA ODANI
A1 SHREE RAM SINGH
A1 HIROYUKI TSUCHIYA
A1 ROBERT M. HOFFMAN
YR 2020
UL http://cgp.iiarjournals.org/content/17/3/217.abstract
AB Background/Aim: We have previously developed a novel bone-targeting platinum compound, 3Pt, and showed that it has strong inhibitory activity against osteosarcoma cells and orthotopic cell-line xenograft mouse models. In the present report, we compared the efficacy of 3Pt to cisplatinum (CDDP) in a CDDP-resistant relapsed osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model. Patients and Methods: The tumor of a patient with osteosarcoma of the distal femur was treated with CDDP-based chemotherapy followed by surgery. The surgical specimen was used to establish a PDOX model. An osteosarcoma cell line was also established from the original patient tumor. Osteosarcoma cell viability was assessed with the WST-8 assay and the IC50 values were calculated. The PDOX models were randomized into three groups: untreated control, CDDP-treated group, and 3Pt-treated group. Tumor size and body weight were measured twice a week. Results: 3Pt had a strong concentration-dependent cytocidal effect in vitro. The IC50 value of 3Pt was significantly lower than that of CDDP. On day 14 of the treatment, 3Pt caused a significantly greater tumor growth inhibition compared to the untreated control and CDDP-treated mice. Conclusion: 3Pt is a promising clinical candidate for the treatment of recalcitrant osteosarcoma.